Anorexia nervosa (AN) is a psychiatric illness characterized by both distorted self-image and a restriction of energy intake relative to requirements, leading to significantly low body weight, and frequently resulting in severe medical complications. As such, numerous physiological changes in people with AN have been observed, including differences in both immunological and gastrointestinal function during the disease. However, these changes have not yet been related to the cognitive and behavioral symptoms observed during AN. This K23 Mentored Career Development Award proposal is a first step to address this gap in the literature. Our proposed research project will evaluate both immune dysregulation and gut microbiome composition in women with AN and healthy comparison participants. In Aim 1, we characterize the molecular components of inflammation by assessing both basal and innate cytokine production capacity. In Aim 2, we evaluate the composition of the gut microbiome and its relationship to eating disorder symptoms. Lastly we will explore (Aim 3) whether alterations in gut microbiome composition correlate with inflammatory marker levels. The career development portion of this award provides the PI with detailed training in 1) gut microbiome-immune system research; 2) psychopathology research methods necessary to conduct independent research investigating biomarkers in eating disorders; 3) translational science design, implementation and management; and 4) responsible conduct of research. An expert team of mentors and advisors will oversee both research and training aims, including an on-site primary mentor with expertise in eating disorders and translational science, Dr. Carrie McAdams, and an on-site co-mentor with expertise in how gut microbiome modulates host immune responses, Dr. Andrew Koh. Dr. Cynthia Bulik, a scientific advisor, will provide mentorship on relating biomarkers with complex human behaviors seen in psychiatric illness. Two additional scientific advisors, Dr. Robert Haley (expertise in biostatistics in relation to neuroimmunology) and Dr. Larry Borish (expertise on immune function and inflammatory pathways) complete the mentorship team. The research and training outlined in this proposal will provide crucial formal and experiential training to allow the PI, a board certified internist with a strong research background in gastrointestinal physiology and immunology, to develop into an independent translational physician-scientist.